甲状腺激素抵抗综合征一家系TRβ基因突变研究

目的研究一个甲状腺激素抵抗综合征家系甲状腺激素受β（thyroid hormone receptor β，TRβ）基因（TRβ）突变情况。方法提取患者及14名家系成员、7名健康对照的外周血基因组DNA，PCR分段扩增刀够基因的第7～10外显子，产物纯化后直接进行DNA测序检测突变。结果测序结果，该家系中5名成员TRβ基因第10外显子的1642位核苷酸发生C→G的转换突变，该突变为错义突变，使该位点所编码的氨基酸由脯氨酸变为丙氨酸（P1453A），同时刀够基因第7外显子的第1020位核苷酸发生C→T的转换突变，该突变为一同义突变，其所编码的氨基酸仍为苯丙氨酸（F245F），两种突变均为杂合子突变。结论在中国人中发现1例TRβ基因突变所致的甲状腺激素抵抗综合征家系。

Study on TRβ gene mutation in a thyroid hormone resistance syndrome family

OBJECTIVE: To detect the gene mutation of thyroid hormone receptor beta (TR beta) in a family with thyroid hormone resistance syndrome. METHODS: The genomic DNA was extracted from peripheral blood leukocytes of the patient, 14 family members and 7 healthy subjects. The exons 7-10 of TR beta gene were amplified by PCR. The products of PCR were purified and sequenced directly to detect the gene mutation. RESULTS: Five members of this family were confirmed to have the C to G transition mutation at nucleotide 1642 site within exon 10 of TR beta gene, which was a missense mutation causing the substitution of Proline to Alanine (P453A); and also to have the C to T transition mutation at nucleotide 1020 within exon 7 of TR beta gene, which was a synonymous mutation that didn't cause the change of amino acid at this position (F245F). The two mutations were heterozygote. No mutation in the exons 7-10 of TR beta gene were identified in other family members. CONCLUSION: A family with thyroid hormone resistance syndrome caused by TR beta gene mutation is first founded in Chinese people.